Evaluation of Granulated Lactose as a Carrier for Dry Powder Inhaler Formulations 2: Effect of Drugs and Drug Loading

Abstract

Previously, granulated lactose carriers were shown to improve uniformity and aerosolization of a low-dose model drug. In the present study, the blending uniformity and aerosol dispersion performance were assessed for 2 model drugs salbutamol sulfate (SS) and rifampicin (RIF), blended at high loadings (10% or 30% drug) with granulated lactose carriers. The model drug powders differed in particle size distribution, morphology, density, and surface energies. Content uniformity of RIF blends was better than that of SS. Aerosolization studies showed that all blend formulations had acceptable emitted fractions (>70%). The SS blends showed low induction-port deposition (6%-10%) compared to RIF (5%-30%). This difference was greater at high flow rates. At 90 L/min, the low induction port deposition of SS blends allowed high fine particle fraction (FPF) of 73%-81%, whereas the FPF of the RIF blends was around 43%-45% with higher induction port deposition. However, SS blends exhibited strong flow rate-dependent performance. Increasing the flow rate from 30 L/min to 90 L/min increased SS FPF from approximately 20% to 80%. Conversely, RIF blends were flow rate and drug loading independent. It was concluded that the aerosolization of high drug-loaded dry powder inhaler formulations using granulated lactose, particularly flow rate dependency, varies with active pharmaceutical ingredient properties.

Assessment of Dry Powder Inhaler Carrier Targeted Design: A Comparative Case Study of Diverse Anomeric Compositions and Physical Properties of Lactose

“…These large spaces might have provided shelter for the API agglomerates (and not single particles), protecting them from dispersion forces . Literature reports indicate that when using the Aerolizer, the former results in drug detachment being predominately dependent on mechanical forces (instead of dispersion forces), which are minimal when smaller carriers are used. , This leads to the drug not being detached from the carrier and a consequent higher emitted dose being found for the LHα-sph adhesive mixtures as well as a greater MMAD (due to the contribution of the API particles that were susceptible to dispersion forces and that detach from the clefts/pores of the carrier as agglomerates, but for which the mechanical forces generated are not enough to break them up). The findings by Wong and Pilpel also reasonably explain the superior in vitro aerosolization performance of Lβ (a carrier with elongated shape, higher density, and greater SSA) when compared to the other carriers tested in this work.…”

Engineering of konjac glucomannan into respirable microparticles for delivery of antitubercular drugs

“…Additionally, the convexity of microparticles was found to reach a value of 0.99 for all formulations, which is close to the maximum value of 1. This is a good indicator for the aerosolisation properties of KGM microparticles, as some studies demonstrate that appropriate surface convexity is critical to improve microparticle dispersion and prevent agglomeration phenomena (Du et al, 2017;Peng et al, 2016). The size and shape of the microparticles (Table 3) were corroborated by the SEM analysis of KGM microparticles.…”

“…The present work demonstrates that, as a whole, KGM microparticles possess suitable properties for deep lung delivery. The morphology of the particles contributes positively to this effect as the convexity, previously described in section 3.2, improves the dispersibility of the particles for inhalation to the deeper zones of the lungs (Du et al, 2017;Peng et al, 2016). This means that the former may have a greater propensity to deposit powder in the lower airways, and is reflected in a higher FPF (Table 5) which is derived from the impactor data.…”

Enhanced Aerosolization of High Potency Nanoaggregates of Voriconazole by Dry Powder Inhalation

“…However, carrier based DPI formulations are generally low drug potency. Also, many factors, such as particle size, size distribution, and surface morphology , of carrier particles, influence the powder aerosol performance during aerosolization, and such factors have negative effects on deposited dose uniformity . By using TFF, the maximum aerosol performance of TFF-VCZ-MAN nanoaggregates was attained with as low as 3% (w/w) mannitol; therefore, the potency of optimized TFF-VCZ-MAN powder formulation can be up to 97% (w/w).…”

“…Also, many factors, such as particle size, 52 size distribution, 53 and surface morphology 52,54 of carrier particles, influence the powder aerosol performance during aerosolization, and such factors have negative effects on deposited dose uniformity. 55 By using TFF, the maximum aerosol performance of TFF-VCZ-MAN nanoaggregates was attained with as low as 3% (w/w) mannitol; therefore, the potency of optimized TFF-VCZ-MAN powder formulation can be up to 97% (w/w). This high drug potency with a very low level of excipient requires less powder to be delivered, and the issues, such as low potency and deposited dose nonuniformity, generally caused by carriers can be eliminated.…”